Dose Escalation Pan-FGFR (Fibroblast Growth Factor Receptor) Inhibitor (Rogaratinib)

NCT ID: NCT01976741

Last Updated: 2021-05-06

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 168 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-12-30
• Study Completion Date: 2020-01-09

Brief Summary

• This was the first study where BAY1163877 was given to humans. Impact of the study was to evaluate if patients with advanced solid cancers show advanced clinical benefit under the treatment with the pan FGFR inhibitor. Patients (all comers) received the study drug treatment in a dose-escalation scheme (no placebo group) to determine the safety, tolerability and maximum tolerated dose (MTD) of BAY1163877. The relative bioavailability of liquid service formulation and tablets was determined.
• After the MTD was defined patients with solid tumors (all comers), lung cancer (lung adenocarcinoma & squamous non-small cell lung cancer), head and neck cancer or bladder cancer was enrolled according to their FGFR expression profile (biomarker stratification).
• The study also assessed the pharmacokinetics, biomarker status, pharmacodynamic parameters and tumor response of BAY1163877.
• BAY1163877 was given twice daily as oral application. Treatment was stopped if the tumor continued to grow, if side effects, which the patient cannot tolerate, occurred or if the patient decided to exit treatment.

Conditions

Neoplasms

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Rogaratinib total dose escalation

Participants with any type of solid tumor received escalating doses of Rogaratinib oral solution or tablet. The actual dose-escalation cohorts were 100 mg (50 mg BID), 200 mg (100 mg BID), 400 mg (200 mg BID), 800 mg (400 mg BID), 1200 mg (600 mg BID), and 1600 mg (800 mg BID). The participants in the 100 mg and 200 mg dose-escalation cohorts received oral solution and the participants in all the subsequent dose-escalation cohorts received tablet. And as an exception, on C1D-3 in the 200 mg dose-escalation cohort, the participants received tablet instead of oral solution.

Group Type: EXPERIMENTAL

Rogaratinib (BAY1163877) oral solution

Intervention Type: DRUG

Participants received Rogaratinib oral solution as a single dose on Cycle 1 Day 1 (C1D1) and twice daily (BID) from Cycle 1 Day 3 (C1D3) onward for the remaining 19 days of Cycle 1. For subsequent cycles, study drug was administered twice daily for 21 days each Cycle.

Rogaratinib (BAY1163877) oral tablet

Intervention Type: DRUG

Participants received Rogaratinib oral tablet as a single dose on C1D1 and BID from C1D3 onward for the remaining 19 days of Cycle 1. For subsequent cycles, study drug was administered twice daily for 21 days each Cycle.

Rogaratinib dose expansion (All Comers)

Participants with cancer types other than bladder cancer (BC), squamous cell carcinoma of the head and neck (SCCHN), and squamous non-small cell lung cancer (sqNSCLC) received 800 mg Rogaratinib oral tablet b.i.d.

(1600 mg/day) in 21-days cycles.

Group Type: EXPERIMENTAL

Rogaratinib (BAY1163877) 800 mg BID

Intervention Type: DRUG

Participants received Rogaratinib 800 mg oral tablet as a single dose on C1D1 and BID (in total 1600 mg) from C1D3 onward for the remaining 19 days of Cycle 1. For subsequent cycles, study drug was administered twice daily for 21 days each Cycle.

Rogaratinib dose expansion (BC)

Participants with bladder cancer (BC) received 800 mg Rogaratinib oral tablet b.i.d. (1600 mg/day) in 21-days cycles.

Group Type: EXPERIMENTAL

Rogaratinib (BAY1163877) 800 mg BID

Intervention Type: DRUG

Participants received Rogaratinib 800 mg oral tablet as a single dose on C1D1 and BID (in total 1600 mg) from C1D3 onward for the remaining 19 days of Cycle 1. For subsequent cycles, study drug was administered twice daily for 21 days each Cycle.

Rogaratinib dose expansion (SCCHN)

Participants with squamous cell carcinoma of the head and neck (SCCHN) received 800 mg Rogaratinib oral tablet b.i.d. (1600 mg/day) in 21-days cycles.

Group Type: EXPERIMENTAL

Rogaratinib (BAY1163877) 800 mg BID

Intervention Type: DRUG

Participants received Rogaratinib 800 mg oral tablet as a single dose on C1D1 and BID (in total 1600 mg) from C1D3 onward for the remaining 19 days of Cycle 1. For subsequent cycles, study drug was administered twice daily for 21 days each Cycle.

Rogaratinib dose expansion (sqNSCLC)

Participants with squamous non-small cell lung cancer (sqNSCLC) received 800 mg Rogaratinib oral tablet b.i.d. (1600 mg/day) in 21-days cycles.

Group Type: EXPERIMENTAL

Rogaratinib (BAY1163877) 800 mg BID

Intervention Type: DRUG

Participants received Rogaratinib 800 mg oral tablet as a single dose on C1D1 and BID (in total 1600 mg) from C1D3 onward for the remaining 19 days of Cycle 1. For subsequent cycles, study drug was administered twice daily for 21 days each Cycle.

Interventions

Rogaratinib (BAY1163877) oral solution

Participants received Rogaratinib oral solution as a single dose on Cycle 1 Day 1 (C1D1) and twice daily (BID) from Cycle 1 Day 3 (C1D3) onward for the remaining 19 days of Cycle 1. For subsequent cycles, study drug was administered twice daily for 21 days each Cycle.

Intervention Type: DRUG

Rogaratinib (BAY1163877) oral tablet

Participants received Rogaratinib oral tablet as a single dose on C1D1 and BID from C1D3 onward for the remaining 19 days of Cycle 1. For subsequent cycles, study drug was administered twice daily for 21 days each Cycle.

Intervention Type: DRUG

Rogaratinib (BAY1163877) 800 mg BID

Participants received Rogaratinib 800 mg oral tablet as a single dose on C1D1 and BID (in total 1600 mg) from C1D3 onward for the remaining 19 days of Cycle 1. For subsequent cycles, study drug was administered twice daily for 21 days each Cycle.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• For dose escalation: Participants with any type of solid tumor (all comer) were eligible for dose escalation and dose expansion at MTD in Part 1; Participants enrolled for dose expansion (MTD expansion cohort "all comer") were stratified according to high fibroblast growth factor receptor (FGFR) expression levels / FGFR mutation using archival or fresh tumor biopsy material
• For expansion cohorts: Participants were eligible for Part 2 only if they have histological or cytological confirmed squamous non-small cell lung cancer (sqNSCLC), lung adenocarcinoma, head and neck cancer or bladder cancer (BC). All participants in Part 2 were stratified according to high FGFR expression levels FGFR mutation using archival or fresh tumor biopsy specimen. BC participants with low overall FGFR expression levels could be included if activating FGFR3 (FGFR tyrosine kinases 3) mutations were confirmed
• Participants must have measurable disease (Response evaluation criteria in solid tumors (RECIST 1.1))
• Eastern Cooperative Oncology Group (ECOG) Performance Status 0 - 2
• Bone marrow, liver and renal functions as assessed by adequate laboratory methods to be conducted within 7 days prior to starting study Treatment
• Glomerular filtration rate (GFR) ≥ 30 mL/min/1.73 m^2 according to the modified diet in renal disease (MDRD) abbreviated formula

Exclusion Criteria

• Previous treatment with anti-FGFR directed therapies (e.g. receptor tyrosine kinase inhibitors or FGFR-specific antibodies)
• Concomitant therapies that cannot be discontinued or switched to a different medication prior to study entry that are known to increase serum phosphate levels are not permitted within 4 weeks prior to start of study treatment)
• Anticancer chemotherapy or immunotherapy during the study or within 5-halflives prior to start of study treatment. Mitomycin C, nitrosoureas or monoclonal antibodies with anticancer activity (e.g. bevacizumab or cetuximab etc.) should not be given within 6 weeks before starting to receive study treatment or within 6 weeks of pre-treatment biopsy for biomarker (p-ERK1/2) studies

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Bayer

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Bayer Study Director

Role: STUDY_DIRECTOR

Bayer

Locations

Chicago, Illinois, United States

Chicago, Illinois, United States

Pittsburgh, Pennsylvania, United States

Besançon, , France

Créteil, , France

Dijon, , France

Lille, , France

Lyon, , France

Heidelberg, Baden-Wurttemberg, Germany

Tübingen, Baden-Wurttemberg, Germany

Weiden, Bavaria, Germany

Würzburg, Bavaria, Germany

Cologne, North Rhine-Westphalia, Germany

Essen, North Rhine-Westphalia, Germany

Dresden, Saxony, Germany

Hamburg, , Germany

Magdeburg, , Germany

Singapore, , Singapore

Singapore, , Singapore

Seoul, , South Korea

Seoul, , South Korea

Seoul, , South Korea

Barcelona, , Spain

Madrid, , Spain

Madrid, , Spain

Valencia, , Spain

Sankt Gallen, Canton of St. Gallen, Switzerland

Chur, Kanton Graubünden, Switzerland

Geneva, , Switzerland

Countries

United States; France; Germany; Singapore; South Korea; Spain; Switzerland

References

Schuler M, Cho BC, Sayehli CM, Navarro A, Soo RA, Richly H, Cassier PA, Tai D, Penel N, Nogova L, Park SH, Schostak M, Gajate P, Cathomas R, Rajagopalan P, Grevel J, Bender S, Boix O, Nogai H, Ocker M, Ellinghaus P, Joerger M. Rogaratinib in patients with advanced cancers selected by FGFR mRNA expression: a phase 1 dose-escalation and dose-expansion study. Lancet Oncol. 2019 Oct;20(10):1454-1466. doi: 10.1016/S1470-2045(19)30412-7. Epub 2019 Aug 9.

Reference Type: RESULT

PMID: 31405822 (View on PubMed)

Grunewald S, Politz O, Bender S, Heroult M, Lustig K, Thuss U, Kneip C, Kopitz C, Zopf D, Collin MP, Boemer U, Ince S, Ellinghaus P, Mumberg D, Hess-Stumpp H, Ziegelbauer K. Rogaratinib: A potent and selective pan-FGFR inhibitor with broad antitumor activity in FGFR-overexpressing preclinical cancer models. Int J Cancer. 2019 Sep 1;145(5):1346-1357. doi: 10.1002/ijc.32224. Epub 2019 Mar 13.

Reference Type: RESULT

PMID: 30807645 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2013-002155-15

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

16443

Identifier Type: -

Identifier Source: org_study_id